tbuckley/cabot-search huggingface dataset:
Transitioning of People With Type 1 Diabetes From Multiple Daily Injections and Self-Monitoring of Blood Glucose Directly to MiniMed 780G Advanced Hybrid Closed-Loop System: A Two-Center, Randomized, Controlled Study
Authors: Bartłomiej Matejko, Anna Juza, Beata Kieć-Wilk, Katarzyna Cyranka, Sabina Krzyżowska, Xiaoxiao Chen, Ohad Cohen, Julien Da Silva, Maciej T. Malecki, Tomasz Klupa
Journal: Diabetes Care (2022)

The aim of this study was to evaluate the outcomes of transitioning to the MiniMed 780G advanced hybrid closed-loop (AHCL) system in adult individuals with type 1 diabetes mellitus (T1DM) naive to continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) technologies.This was a two-center, randomized, controlled, parallel-group trial with evaluation of individuals with T1DM aged 26-60 years managed with multiple daily injections (MDI) and self-monitoring of blood glucose (BGM) with HbA1c <10%.A total of 41 participants were recruited and randomized to either the AHCL (n = 20) or the MDI+BGM (n = 21) group, and 37 participants (mean ± SD age 40.3 ± 8.0 years, duration of diabetes 17.3 ± 12.1 years, BMI 25.1 ± 3.1 kg/m2, HbA1c 7.2 ± 1.0%) completed the study. Time spent with glucose levels in target range increased from 69.3 ± 12.3% at baseline to 85.0 ± 6.3% at 3 months in the AHCL group, while remaining unchanged in the control group (treatment effect 21.5% [95% CI 15.7, 27.3]; P < 0.001). The time with levels below range (<70 mg/dL) decreased from 8.7 ± 7.3% to 2.1 ± 1.7% in the AHCL group and remained unchanged in the MDI+BGM group (treatment effect -4.4% [95% CI -7.4, -2.1]; P < 0.001). Participants from the AHCL group also had significant improvements in HbA1c levels (treatment effect -0.6% [95% CI -0.9, -0.2]; P = 0.005) and in quality of life (QoL) in specific subscales compared with the MDI+BGM group.People with T1DM naive to CSII and CGM technologies initiating AHCL significantly and safely improved their glycemic control, as well as their QoL and psychological well-being.
Effect of State-Led Delivery System and Payment Reforms on Population-Level Detection and Management of Diabetes
Authors: Hector P. Rodriguez, Brent D. Fulton, Aryn Z. Phillips, Karl Rubio
Journal: Diabetes Care (2022)

The Centers for Medicare and Medicaid Services State Innovation Models (SIM) initiative has invested more than $1 billion to test state-led delivery system and payment reforms that can affect diabetes care management. We examined whether SIM implementation between 2013 and 2017 was associated with diagnosed diabetes prevalence or with hospitalization or 30-day readmission rate among diagnosed adults.The quasiexperimental design compared study outcomes before and after the SIM initiative in 12 SIM states versus five comparison states using difference-in-differences (DiD) regression models of 21,055,714 hospitalizations for adults age ≥18 years diagnosed with diabetes in 889 counties from 2010 to 2017 across the 17 states. For readmission analyses, comparative interrupted time series (CITS) models included 11,812,993 hospitalizations from a subset of nine states.Diagnosed diabetes prevalence changes were not significantly different between SIM states and comparison states. Hospitalization rates were inconsistent across models, with DiD estimates ranging from -5.34 to -0.37 and from -13.16 to 0.92, respectively. CITS results indicate that SIM states had greater increases in odds of 30-day readmission during SIM implementation compared with comparison states (round 1: adjusted odds ratio [AOR] 1.07; 95% CI 1.04, 1.11; P < 0.001; round 2: AOR 1.06; 95% CI 1.03, 1.10; P = 0.001).The SIM initiative was not sufficiently focused to have a population-level effect on diabetes detection or management. SIM states had greater increases in 30-day readmission for adults with diabetes than comparison states, highlighting potential unintended effects of engaging in the multipayer alignment efforts required of state-led delivery system and payment reforms.
Association of Estimated Time-in-Range Capillary Glucose Levels Versus HbA1c With Progression of Microvascular Complications in the Diabetes Control and Complications Trial
Authors: John M. Lachin, Ionut Bebu, Xiaoyu Gao, David M. Nathan, Bernard Zinman
Journal: Diabetes Care (2022)

Estimated time in range (eTIR) obtained from DCCT glucose profiles (pre- and postprandial and bedtime) was recently reported to be associated with microvascular outcomes and was recommended as a clinical trial outcome, but without consideration of HbA1c.The associations of eTIR with diabetic retinopathy and microalbuminuria were assessed without and with adjustment for HbA1c and baseline covariates.Adjusted for HbA1c and covariates, eTIR was marginally significantly associated with retinopathy in the full cohort (hazard ratio [HR] 1.12 per 10% lower eTIR [95% CI 1.0, 1.26], P = 0.042). Conversely, HbA1c was significantly associated with both outcomes (HR ≥1.19 per 0.5% higher HbA1c, P ≤ 0.0002) in five of six adjusted analyses.The association of eTIR with complications is largely explained by its correlation with HbA1c. HbA1c, not eTIR or continuous glucose monitoring TIR, remains the preferred outcome in clinical studies of type 1 diabetes complications.
The Fast-Glycator Phenotype, Skin Advanced Glycation End Products, and Complication Burden Among People With Type 1 Diabetes
Authors: Alberto Maran, Mario Luca Morieri, Daniele Falaguasta, Angelo Avogaro, Gian Paolo Fadini
Journal: Diabetes Care (2022)

Existence of a fast-glycator phenotype among people with type 1 diabetes (T1D) is debated. Routine use of glucose sensors allows the comparison of long-term average glucose levels with laboratory HbA1c values. We herein evaluated whether participants with T1D and HbA1c values higher than their glucose management indicator (GMI) had greater accumulation of advanced glycation end products (AGEs) and chronic complications.We included participants with T1D using the intermittently scanned continuous glucose monitoring system consecutively for at least 90 days and having a laboratory-determined HbA1c at the end of observation. Skin AGEs were estimated using the skin autofluorescence (SAF) method. The complication burden was assessed by a standardized screening. The fast-glycator phenotype was defined as having a GMI to HbA1c ratio <0.9.We included 135 individuals with T1D (58% men; mean age, 44.4 years) with a mean diabetes duration of 21 years and a mean HbA1c value of 7.7%. Thirty (22.2%) were defined as having the fast-glycator phenotype. As expected, fast glycators had higher HbA1c (8.6% vs. 7.5%; P < 0.001) with similar 90-day mean glucose level (172 vs. 168 mg/dL; P = 0.52). Fast glycators had higher SAF than did other participants (2.5 vs. 2.1 arbitrary units; P = 0.005) and had a significantly higher prevalence of dyslipidemia (73% vs. 44%; P = 0.005), macroangiopathy (38% vs. 9%; P = 0.001), albuminuria (25% vs. 7%; P = 0.038), and retinopathy (61% vs. 38%; P = 0.022). After adjusting for age and dyslipidemia, the fast-glycator phenotype remained significantly associated with macroangiopathy (odds ratio 3.72; 95% CI 1.22-11.4).In T1D, a fast-glycator phenotype defined by the GMI to HbA1c ratio is characterized by elevated skin AGEs and is associated with the complication burden.
hiPSC-derived bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukemia
Authors: Deepali Pal, Helen Blair, Jessica Parker, Sean Hockney, Melanie Beckett, Mankaran Singh, Ricky Tirtakusuma, Ryan Nelson, Hesta McNeill, Sharon H. Angel, Aaron Wilson, Salem Nizami, Sirintra Nakjang, Peixun Zhou, Claire Schwab, Paul Sinclair, Lisa J. Russell, Jonathan Coxhead, Christina Halsey, James M. Allan, Christine J. Harrison, Anthony V. Moorman, Olaf Heidenreich, Josef Vormoor
Journal: Cell Reports Medicine (2022)

Leukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies. We reveal that mesenchymal (iMSC) and vascular niche-like (iANG) hiPSC-derived cells support ex vivo proliferation of patient-derived leukemia cells, affect dormancy, and mediate treatment resistance. iMSCs protect dormant and cycling blasts against dexamethasone, while iANGs protect only dormant blasts. Leukemia proliferation and protection from dexamethasone-induced apoptosis is dependent on cancer-niche interactions mediated by CDH2. Consequently, we test CDH2 antagonist ADH-1 (previously in Phase I/II trials for solid tumors) in a very aggressive patient-derived xenograft leukemia mouse model. ADH-1 shows high in vivo efficacy; ADH-1/dexamethasone combination is superior to dexamethasone alone, with no ADH-1-conferred additional toxicity. These findings provide a proof-of-concept starting point to develop improved, potentially safer therapeutics targeting niche-mediated cancer dependencies in blood cancers.
Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020
Authors: Kartik K. Venkatesh, Courtney D. Lynch, Maged M. Costantine, Carl H. Backes, Jonathan L. Slaughter, Heather A. Frey, Xiaoning Huang, Mark B. Landon, Mark A. Klebanoff, Sadiya S. Khan, William A. Grobman
Journal: JAMA (2022)

Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging.To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity.Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US.Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White.Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated.Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment.From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.
Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [18F]AlF-FAPI-74
Authors: Iris K. Lee, Estela Noguera-Ortega, Zebin Xiao, Leslie Todd, John Scholler, Decheng Song, Maria Liousia, Katheryn Lohith, Kexiang Xu, Kimberly J. Edwards, Michael D. Farwell, Carl H. June, Steven M. Albelda, Ellen Puré, Mark A. Sellmyer
Journal: Clinical Cancer Research (2022)

Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting of solid tumors with CAR T cells has been limited by a lack of durable responses and reports of toxicities. Our understanding of the limited therapeutic efficacy in solid tumors could be improved with quantitative tools that allow characterization of CAR T-targeted antigens in tumors and accurate monitoring of response.
New Device Okayed for Treating Pulmonary Hypertension in Newborns
Authors: Rita Rubin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sleek Green Car
Authors: Daniel Lawless
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Modulating biomolecular condensates: a novel approach to drug discovery
Authors: Diana M. Mitrea, Matthäus Mittasch, Beatriz Ferreira Gomes, Isaac A. Klein, Mark A. Murcko
Journal: Nature Reviews Drug Discovery (2022)

In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved.
Imaging Glioblastoma Response to Radiotherapy Using 2H Magnetic Resonance Spectroscopy Measurements of Fumarate Metabolism
Authors: Friederike Hesse, Alan J. Wright, Vencel Somai, Flaviu Bulat, Felix Kreis, Kevin M. Brindle
Journal: Cancer Research (2022)

Abstract Early detection of tumor cell death in glioblastoma following treatment with chemoradiation has the potential to distinguish between true disease progression and pseudoprogression. Tumor cell death can be detected noninvasively in vivo by imaging the production of [2,3-2H2]malate from [2,3-2H2]fumarate using 2H magnetic resonance (MR) spectroscopic imaging. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]fumarate metabolism can detect tumor cell death in orthotopically implanted glioblastoma models within 48 hours following the completion of chemoradiation. Following the injection of [2,3-2H2]fumarate into tumor-bearing mice, production of [2,3-2H2]malate was measured in a human cell line–derived model and in radiosensitive and radioresistant patient-derived models of glioblastoma that were treated with temozolomide followed by targeted fractionated irradiation. The increase in the [2,3-2H2]malate/[2,3-2H2]fumarate signal ratio posttreatment, which correlated with histologic assessment of cell death, was a more sensitive indicator of treatment response than diffusion-weighted and contrast agent–enhanced 1H MRI measurements, which have been used clinically to detect responses of glioblastoma to chemoradiation. Overall, early detection of glioblastoma cell death using 2H MRI of malate production from fumarate could help improve the clinical evaluation of response to chemoradiation. Significance: 2H magnetic resonance imaging of labeled fumarate metabolism can detect early evidence of tumor cell death following chemoradiation, meeting a clinical need to reliably detect treatment response in glioblastoma.
<i>IDH1/2</i>wildtype gliomas grade 2 and 3 with molecular glioblastoma-like profile have a distinct course of epilepsy compared to<i>IDH1/2</i>wildtype glioblastomas
Authors: Mark P van Opijnen, C Mircea S Tesileanu, Linda Dirven, Pim B van der Meer, Maarten M J Wijnenga, Arnaud J P E Vincent, Marike L D Broekman, Hendrikus J Dubbink, Johan M Kros, Sjoerd G van Duinen, Marion Smits, Pim J French, Martin J van den Bent, Martin J B Taphoorn, Johan A F Koekkoek
Journal: Neuro-Oncology (2022)

Abstract Background IDH1/2 wildtype (IDHwt) glioma WHO grade 2 and 3 patients with pTERT mutation and/or EGFR amplification and/or + 7/−10 chromosome gain/loss have a similar overall survival time as IDHwt glioblastoma patients, and are both considered glioblastoma IDHwt according to the WHO 2021 classification. However, differences in seizure onset have been observed. This study aimed to compare the course of epilepsy in the 2 glioblastoma subtypes. Methods We analyzed epilepsy data of an existing cohort including IDHwt histologically lower-grade glioma WHO grade 2 and 3 with molecular glioblastoma-like profile (IDHwt hLGG) and IDHwt glioblastoma patients. Primary outcome was the incidence proportion of epilepsy during the disease course. Secondary outcomes included, among others, onset of epilepsy, number of seizure days, and antiepileptic drug (AED) polytherapy. Results Out of 254 patients, 78% (50/64) IDHwt hLGG and 68% (129/190) IDHwt glioblastoma patients developed epilepsy during the disease (P = .121). Epilepsy onset before histopathological diagnosis occurred more frequently in IDHwt hLGG compared to IDHwt glioblastoma patients (90% vs 60%, P &amp;lt; .001), with a significantly longer median time to diagnosis (3.5 vs 1.3 months, P &amp;lt; .001). Median total seizure days was also longer for IDHwt hLGG patients (7.0 vs 3.0, P = .005), and they received more often AED polytherapy (32% vs 17%, P = .028). Conclusions Although the incidence proportion of epilepsy during the entire disease course is similar, IDHwt hLGG patients show a significantly higher incidence of epilepsy before diagnosis and a significantly longer median time between first seizure and diagnosis compared to IDHwt glioblastoma patients, indicating a distinct clinical course.
A machine learning framework supporting prospective clinical decisions applied to risk prediction in oncology
Authors: Lorinda Coombs, Abigail Orlando, Xiaoliang Wang, Pooja Shaw, Alexander S. Rich, Shreyas Lakhtakia, Karen Titchener, Blythe Adamson, Rebecca A. Miksad, Kathi Mooney
Journal: npj Digital Medicine (2022)

We present a general framework for developing a machine learning (ML) tool that supports clinician assessment of patient risk using electronic health record-derived real-world data and apply the framework to a quality improvement use case in an oncology setting to identify patients at risk for a near-term (60 day) emergency department (ED) visit who could potentially be eligible for a home-based acute care program. Framework steps include defining clinical quality improvement goals, model development and validation, bias assessment, retrospective and prospective validation, and deployment in clinical workflow. In the retrospective analysis for the use case, 8% of patient encounters were associated with a high risk (pre-defined as predicted probability ≥20%) for a near-term ED visit by the patient. Positive predictive value (PPV) and negative predictive value (NPV) for future ED events was 26% and 91%, respectively. Odds ratio (OR) of ED visit (high- vs. low-risk) was 3.5 (95% CI: 3.4-3.5). The model appeared to be calibrated across racial, gender, and ethnic groups. In the prospective analysis, 10% of patients were classified as high risk, 76% of whom were confirmed by clinicians as eligible for home-based acute care. PPV and NPV for future ED events was 22% and 95%, respectively. OR of ED visit (high- vs. low-risk) was 5.4 (95% CI: 2.6-11.0). The proposed framework for an ML-based tool that supports clinician assessment of patient risk is a stepwise development approach; we successfully applied the framework to an ED visit risk prediction use case.
Using the upgrade criteria of the European Psoriasis Consensus is best practice care according to the people-centred healthcare concept of the World Health Organization
Authors: Ulrich Mrowietz, Matthias Augustin
Journal: British Journal of Dermatology (2022)

Journal Article Using the upgrade criteria of the European Psoriasis Consensus is best practice care according to the people‐centred healthcare concept of the World Health Organization Get access Ulrich Mrowietz, Ulrich Mrowietz Psoriasis‐Center, Department of Dermatology University Medical Center Schleswig‐Holstein Campus Kiel Kiel Germany https://orcid.org/0000-0002-9539-0712 Search for other works by this author on: Oxford Academic Google Scholar Matthias Augustin Matthias Augustin German Center for Health Services Research in Dermatology (CVderm), Institute for Health Services Research in Dermatology and Nursing (IVDP) University Medical Center Hamburg‐Eppendorf (UKE) Hamburg Germany Correspondence: Matthias Augustin. Email: m.augustin@uke.de https://orcid.org/0000-0002-4026-8728 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 187, Issue 6, 1 December 2022, Pages 1007–1008, https://doi.org/10.1111/bjd.21827 Published: 01 December 2022